This application claims priority to Great Britain Application No. 0105205.9, filed Mar. 2, 2001 and is a Continuation In Part of U.S. application Ser. No. 09/419,922, filed Oct. 18, 1999 (U.S. Pat. No. 6,274,161), which is a Continuation of application Ser. No. 08/866,517 filed May 30, 1997, which issued as U.S. Pat. No. 5,968,544 on Oct. 19, 1999, which derives priority from Great Britain Application No. 9611356.8, filed May 31, 1996. The entirety of all the above applications are incorporated herein by reference.
This invention relates to compositions for human consumption comprising creatine and creatinine and to a method of providing stable creatine containing compositions.
In the last few years there has been considerable interest among athletes in creatine, which occurs abundantly in skeletal muscle. Creatine plays a pivotal role in the regulation and homeostasis of skeletal muscle energy metabolism and it is now generally accepted that the maintenance of phospho-creatine availability is important to the continuation of muscle force production. Creatine may also be involved in other processes concerned with protein synthesis and hypertrophy of muscle fibres during training. Although creatine synthesis occurs in the liver, kidney and pancreas it has been known for sometime that the oral ingestion of creatine will add to the whole body creatine pool, and it has been shown that the ingestion of 20 to 30 g creatine monohydrate (Cr.H2O) per day for several days can lead to a greater than 20% increase in human skeletal muscle total creatine content. Thus, WO94/02127 discloses the administration of creatine monohydrate in amounts of at least 15 g (or 0.2-0.4 g/kg body weight) per day, for at least 2 days, for increasing muscular strength.
In fact, it was subsequently found that after several days of supplementation (20 g per day) with creatine monohydrate in order to attain initial elevation of the tissue stores, thereafter it takes no more than 2 to 3 g per day to maintain the newly elevated concentration. Supplementation with any bioavailable source of creatine (i.e. creatine supplementation) in an appropriate dose can provide improvements to athletes involved in explosive events, which include all events lasting from a few seconds to a few minutes (such as sprinting, swimming, weight-lifting etc). Endurance performance in events lasting longer than about 30 minutes appear less affected by creatine supplementation except where this involves short periods of increased energy output particularly when the local muscle carbohydrate stores have become depleted. Creatine is a normal food component and is not a drug and its use is not contrary to official regulations. It is possible that the greatest benefits of creatine supplementation are experienced by the elderly, vegetarians or those who eat no meat or fish, since these people tend to have low muscle creatine contents.
Aloe Vera (Aloe barbadensis) is a member of the lily family and is a cactus-like succulent plant that grows in warm frost-free climates. Central American Mexican Indians used Aloe Vera for centuries as a remedy for bums, to prevent blisters, peptic and duodenal ulcers and all types of stomach and intestinal disorders, kidney infections, topical and gastric ulcers as well as to promote longevity. Today Aloe Vera is becoming very popular and its benefits are scientifically recognized.
The main use of Aloe Vera in the past has been to prevent inflammation, particularly to the skin, especially after bums, but there are many other uses. Experiments and research studies have shown that after using Aloe Vera juice, the output of the digestive enzymes and the bacterial population of the intestines are improved. Thus there has been an increasing interest in Aloe Vera extract as a medicament to be taken orally as people become more acquainted with its medicinal properties
Among the several methods of presentation, there is a growing use of Aloe Vera extract in soft drinks which are fruit flavored, and these are quite palatable. The inclusion of creatine in a soft drink would be highly desirable because the Aloe Vera extract drink would be much more beneficial to health than an unsupplemented ordinary fruit drink.
Aloe Vera juice is acidic (commonly about pH 3). It is well known that the creatine molecule is unstable in aqueous solutions at acid or neutral pH, and is converted into the related compound creatinine. This is highly significant as creatinine has no muscle performance-enhancing effect and is excreted from the human body as a waste product in urine. In view of the foregoing, EP 0 669 083 teaches that aqueous drinks for human consumption comprising creatine must be weakly alkaline, in order to limit the conversion of creatine into creatinine, and this has become the generally accepted opinion.
Furthermore, creatine and its derivatives have been used in the past but only for the preparation of products with a meaty or savory flavor. For instance, Tonsbeek (U.S. Pat. No. 3,615,600) discloses and is concerned with artificial flavoring, describing mixtures imparting a meaty flavor to foods. Similary de Rooji (U.S. Pat. No. 4,464,409) is concerned with meat flavoring. Yamazaki (JP-A-59035663) prepares a meat flavor by heating a mixture comprising creatine at pH 5.0-7.0 at a temperature of 80-130xc2x0 C. for 30-120 minutes. Under these conditions most of the creatine is converted to creatinine.
The inventors believe that it would not occur to the persons skilled in the art to add creatinine (used hitherto as a meat or savory flavoring agent) to compositions which were intended to have a flavor (especially a fruit flavor) other than meaty or savory. The person skilled in the art might have expected the addition of creatinine to result in an unpalatable combination of fruit and meat flavors, whereas in fact the inventors have found that the resulting combination does not impart an undesirable meaty flavor.
WO 97/45026 discloses an acidic composition for human consumption comprising creatine and its derivatives, the composition being provided as a dry powder or in liquid or semi-liquid form. The compositions disclosed therein are stable at refrigerated temperatures (4xc2x0 C.) for prolonged periods but stable at ambient temperature for relatively short periods (e.g. up to, but not exceeding, 7 days).
WO 00/74500 discloses compositions comprising creatine and its derivatives suspended in aloe vera gel, which compositions were stable (with respect to the conversion of creatine to creatinine) at room temperature for 2 weeks or more, depending on the initial concentration of creatine in the composition.
Both WO 97/45026 and WO 00/74500 stress the desirability of preventing the conversion of creatine to creatinine, and neither document suggests the deliberate addition of creatinine to a creatine-containing composition intended for human consumption.
It would be a great advantage to present a composition for human consumption, in which the creatine therein was substantially stable, even at acidic pH and at ambient temperatures.
The present invention is concerned with the provision of compositions for human consumption comprising creatine and its derivatives, especially compositions presented in an aqueous medium, more especially compositions (such as drinks) in which creatine is provided in aqueous solution or in which creatine is suspended in an edible supporting matrix.
The term xe2x80x9ccreatinexe2x80x9d as used herein is intended to encompass all bioavailable derivatives of creatine, such as creatine monohydrate, phosphocreatine, and other salts of creatine. Creatine monohydrate is particularly preferred. Accordingly the term xe2x80x9ccreatinexe2x80x9d should be construed broadly where the context permits.
As explained above, it is well known that the creatine molecule in aqueous solution is unstable, especially at acidic pH (i.e. below pH 7), being converted to creatinine (Edgar and Shiver, 1925 J. Am. Chem. Soc., 47, p.1179-1188; Cannan and Shore 1928 Biochem. J. 22, p.920-929). This presents a problem in attempting to provide drinks or other compositions containing creatine in physiologically useful amounts, especially as drinks are usually formulated so as to have a pH below 7.
Edgar and Shiver conducted some investigations into the equilibrium which exists between creatine and creatinine in aqueous solution and, in particular, the effect on the equilibrium position by the use of buffers of different pH. Unfortunately the work of Edgar and Shiver does not offer any useful practical guidance to the person skilled in the art of formulating beverages and other nutritional compositions, for several reasons. Firstly, the publication by Edgar and Shiver is very old and of purely academic interest, would be unlikely to be consulted by a person skilled in the art of formulating beverages, and does not have a direct bearing on the formulation of beverages. Secondly, and most significantly, Edgar and Shiver conducted their experiments using extremely dilute solutions of creatine/creatinine (0.001M, equivalent to 0.0149 g creatine/100 ml, creatine monohydrate having a molecular weight of 149): whilst these are appropriate for purely analytical considerations they have no relevance whatsoever to systems which comprise high concentrations (over 0.15 g creatine monohydrate or equivalent/100 ml) of creatine and are intended to provide physiologically useful amounts of creatine in a beverage. Thirdly, Edgar and Shiver neglected to take account of the change in pH which occurs upon conversion of creatine to creatinine and vice versaxe2x80x94such a change is probably negligible using the very dilute creatine/creatinine mixtures employed by Edgar and Shiver, but would have a significant impact at high concentrations, such as are desirable in a beverage, as the present inventors have discovered. Generally similar comments apply to the equally. old publication by Cannan and Shore.
The obvious solution to the instability of creatine would be simply to increase the initial concentration of creatine in the composition, so that a physiologically useful amount of creatine is present in the composition for a longer time period. However this approach does nothing to prevent or inhibit the conversion of creatine to creatinine. Furthermore, extensive conversion of creatine to creatinine is likely to increase the pH of the composition, as the reaction involves the removal of a hydrogen ion. This may change the palatability and be undesirable to the consumer. Moreover, creatine is not particularly soluble in water (especially at the low temperatures, e.g. 3-5xc2x0 C., at which drinks are usually stored), so there is a finite maximum initial concentration of creatine which cannot be exceeded. In addition, the inclusion of excess creatine is undesirable, as the presence of undissolved creatine in drink formulations is not attractive to consumers. Starting with a solution of creatine would result in a drink with less than the maximum amount of creatine in solution since some of the creatine would be converted to creatinine. The inventors have provided an alternative approach explained below.
In a first aspect the invention provides a composition for human consumption comprising creatine and a quantity of creatinine sufficient to render the creatine therein substantially stable (as defined below) in an aqueous medium.
The creatinine content of the composition is present ab initio, (i.e. upon formation of the final composition), rather than arising during the storage of the composition as a result of the conversion of creatine into creatinine. It will be apparent from the teaching below that, at least in some embodiments, the production of the composition (i.e. processing prior to formation of the final compositions) may involve the deliberate conversion of creatine to creatinine. Stability of the creatine ab initio is desirable commercially, because it allows exact characterisation of the creatine content of the composition (which may, for example, be indicated on packaging and the like) and it allows consumers to calculate the exact dose of creatine consumed.
The composition may be provided as a liquid, a semi-liquid, an edible matrix or a solid for subsequent solution in water. The creatine can be dissolved in water to provide a liquid.
For compositions in which the creatine is suspended in a semi-liquid or a supporting matrix the creatine content for the composition is preferably subjected to a micronisation process (e.g. crushing, pulverising, powdering and the like) prior to incorporation into a semi-liquid or other supporting matrix so that the resulting composition is not unacceptably gritty in texture.
Conveniently the supporting matrix, if present, is a recognised foodstuff, such that a composition in accordance with the invention may take the form of an otherwise conventional foodstuff, supplemented with creatine and creatinine, such that solid creatine becomes suspended in the foodstuff. Examples of foodstuffs which may represent suitable supporting matrices for the composition of the invention include spreadable solids such as dairy or cheese spreads, margarines, caviar (mainly lump fish caviar) spread, and other fish pastes, meat spreads, and the like. Other convenient supporting matrices are those comprising sugars or other carbohydrates, such as liquid or solid honey, molasses, syrup (e.g. corn syrup, glucose syrup), treacle, glycerol or xe2x80x9cMaxim Energy gelxe2x80x9d(trademark).
If desired the viscosity of the solution and/or the composition as a whole may be increased by the addition of viscosifiers, gelling agents and the like. Such components are well-known in the food industry and include, for example, plant-derived polysaccharides, gums and the like such as galactomannans, dextrans, guar gum, locust bean gum, xanthan gum and so on.
Such viscosifiers, gels and the like may take the form of a supporting matrix, if desired. One preferred edible matrix comprises a gel prepared from concentrated Aloe Vera extract: a smooth creamy paste (suitable for packaging in a squeezable tube) may be prepared by mixing 5 gms of creatine with (for example) 60 ml of a concentrated Aloe Vera gel (such as that obtainable from Aloe Commodities Int. Inc., Farmers Branch, Tex. 75234). In addition the supporting matrix may comprise a semi-liquid foodstuff such as a yogurt or other semi-liquid foodstuff.
The present inventors have previously found that the conversion of creatine to creatinine in aqueous solutions can be markedly inhibited by creatinine itself, such that a mixture of creatine and creatinine can quickly reach equilibrium and the creatine becomes substantially stable. Without wishing to be bound by any particular theory, the inventors believe that the explanation for this observation is that the conversion of creatine to creatinine is a reversible reaction. The inventors have now found that, by providing creatine in solution together with an appropriate amount of creatinine the conversion of creatine to creatinine (even in an acidic composition) can be greatly inhibited or even substantially prevented even at ambient (i.e.2-39xc2x0 C.) temperature or above for long periods (30 to 95 days or more). Thus, in some embodiments the composition as a whole may conveniently be selected to be acidic (i.e. have a pH below 7.0) or even alkaline (eg 7.0 to 8.5) without significantly adversely affecting the stability of the creatine content of the composition. In particular the composition desirably has a pH between 2.5 and 8.5, preferably between 3.0 and 7.0 and most preferably between 4.5 and 6.5. Typically the composition has a pH in the range 4.5 to 5.5 which, to the human palate, has a refreshingly sharp taste without being too acidic.
Compositions in accordance with the invention are substantially stable so that creatine may be presented even in acidic formulations, contrary to the teaching of the art, in physiologically useful amounts, following storage for prolonged periods at ambient temperature. A physiologically effective amount of creatine is an amount sufficient to cause a measurable increase in the creatine content of the tissues of a subject following repeated consumption of the composition, relative to an initial baseline level. Methods of measuring the creatine content of the tissues of a subject are known (e.g. Harris, Hultman and Nordesjo (1974) Glycogen, glycolytic intermediates and high energy phosphates in biopsy samples of musculus quadriceps femoris of man at rest. Methods and variance of values. Scand. J. Clin. Lab. Invest. 33, 109-120; Dunnett, Harris and Orme (1991) Reverse phase ion-pairing high performance liquid chromatography of phosphocreatine, creatine and creatinine in equine muscle. Scand J. Clin. Lab. Invest. 51, 137-141).
The term xe2x80x9csubstantially stablexe2x80x9d is herein defined referring to a creatine/creatinine composition in which at least 75% (preferably at least 80%, and more preferably at least 85%) of the creatine in the composition immediately after formulation of the final product is unchanged, and therefore not converted into creatinine, for a period of at least (and preferably more than) 7 days"" storage. The stability of creatine depends on the PH; the latter decreases with increasing temperature. (The xe2x80x9cfinal productxe2x80x9d is the composition produced after all processing and production steps have been completed.)
The inventors have found that a 20xc2x0 C. increase in temperature can decrease the pH by as much as 0.3 units. The temperature range to which the composition will be subjected (eg in a refrigerator or a warehouse) is typically between 2 to 50xc2x0 C. Desirably, the composition will be sufficiently stable such that 75% of the creatine remains over the temperature range of 2 to 50xc2x0 C. following a period of at least 30 days, more preferably 60 days, and most preferably at least 120 days, during storage. In order to specify stability it is necessary to specify the pH (which must be measured at the temperature at which the solution will be stored) at which stability is required. The pH is altered by warming or cooling of a buffered solution and over the range of temperatures that a solution may be stored the equilibrium ratio of creatine: creatinine can vary greatly. However, if the composition is stable at 50xc2x0 C. then its creatine content will not decrease on storage at a lower temperature.
As mentioned above, the mole:mole ratio of creatinine to creatine to achieve stability of creatine, is found to depend on the pH of the solution and ranges from 1:2 for pH 7 to 3.8:1 for pH 4.25. It is preferred that the mole:mole ratio of creatinine to creatine is not more than 10:1. More preferred is a ratio of not more than 5:1. Most preferred is a ratio of creatinine to creatine which is not too high (since creatinine is an inactive ingredient) and the most preferred pH is 5 to 7 where the mole:mole ratio of creatinine to creatine ranges from about 1.2:1 to 1:2.
For the purpose of the invention, the creatinine can be added to the creatine as a pure substance or the creatinine can be manufactured in situ by heating creatine in solution, preferably at low pH e.g. pH 2 to 3. It is most convenient for the solution to be heated and held for at least 30 minutes at 90xc2x0 C. or more because these are the conditions often used for the sterilisation of a liquid for commercial sale. (Alternatively, an equivalent sterilising xe2x80x9cheat dosexe2x80x9d can be provided by heating to greater temperatures for shorter periods of time or vice versa.) In other embodiments, creatinine can be prepared by heating a solution of creatine for several hours at pH 2 to 3 and then adding it to a solution of creatine at higher pH (e.g. pH 7) and adjusting the final mix to the desired pH (e.g. pH 5). If required the solution can then be re-sterilised under the above-mentioned conditions. In this method of preparation, there may be little or no further conversion of creatine to creatinine and stability is ensured immediately after mixing the two solutions. This method has advantages because creatine is not very soluble in water when chilled in a refrigerator, whereas creatinine is much more soluble. By producing a stable solution of creatine by this method it is possible to formulate a drink which contains a relatively larger quantity of stable creatine than could be achieved otherwise. Thus by this means, it is possible to produce a drink suitable for refrigeration which contains up to 1.2 g creatine/100 ml (or 1.4 g creatine monohydrate) or a drink suitable for storage at ambient temperatures of 18 to 25xc2x0 C. which contains up to 1.5 g creatine/100 ml (or 1.7 g creatine monohydrate/100 ml).
A further advantage of the invention is that it enables the provision of a composition which comprises the maximum concentration of dissolved creatine available (under the relevant conditions of pH and temperature), but using the least amount of creatine necessary, in a stable formulation, and so does not require the use of excess creatine.
A preferred embodiment of the invention is an aqueous drink, especially one at acid pH (i.e. below pH7), and in particular which has a pH in the range 4-6.5, especially 4.5-5.5, and which comprises at least 0.15 g creatine (or creatine monohydrate and the like) per 100 ml. Preferably the drink comprises at least 0.3 g creatine (or creatine monohydrate and the like) per 100 ml, more preferably at least 0.4 g per 100 ml and most preferably at least 0.5 g per 100 ml.
The composition may comprise a solution of creatine and creatinine in water without additional components (such as for example flavoring) as a solution in water e.g. mineral water or carbonated water using processes which are well known to those skilled in the art.
Preferably however the composition may comprise one or more further components to improve its palatability, stability, flavor or nutritive quality. These further components may include electrolytes, or may be selected from the group consisting of: vitamins, lipids, proteins, carbohydrates, polyols (such as ethylene glycol, glycerol, sorbitol etc.), amino acids, trace elements, colorings, flavors, artificial sweeteners, natural health and performance improving substances, anti-oxidants, stabilizers, preservatives, and buffers.
Vitamins may be included with advantage in the composition of the invention. These may be added in amounts which range from 20 to 100% of their recommended daily allowance (RDA). The following are typical of those which are useful: vitamin E, vitamin C, thiamin, riboflavin, niacin, vitamin B6, folacin, vitamin B12, biotin, and pantothenic acid.
In some cases a lipid component may be desirable. The protein content (if any) may be present as soya or milk proteins (e.g. whey or casein). The carbohydrate content (if any) or the composition may be present as starch (particularly soluble starch) and/or sugars. The sugars which may be present in the composition include glucose, fructose, sucrose, lactose and maltose.
Artificial sweeteners which can be used include Aspartame, Acesulfam K, Saccharin and Cyclamate. Almost any desired flavoring can be added, most preferably fruity flavors such as berry, lemon, orange, papaya and grapefruit. However, at less acidic pHs (e.g. over 5.0) other flavors such as chocolate, malt, caramel and other flavors suitable for xe2x80x9cmilkyxe2x80x9d drinks can be used. Citric acid may also be used as an acidulant and citrate and phosphate (e.g. sodium citrate or phosphate) as a buffering agent. Other buffering agents may be used to regulate the acidity of the drink. Also other natural health improving substances may be added in physiologically active amounts. The following are typical of those which are useful: Pau D""Arco tea, Ginseng, Suma tea, Ginkgo, bee pollen, myrrh, hydroxy-methy-butyrate, glutamine, di- tri-, and polypeptides containing glutamine, ribose, caffeine, and lipoic acid.
Preservatives can be provided typically by potassium benzoate and/or potassium sorbate.
Coloring can be provided, typically by using a cold water soluble colorant such as beta-carotene. Other suitable colorings will be apparent to those skilled in the art.
A clouding agent may be included in the composition, if desired, to improve the appearance of the composition.
The mineral and trace elements can also be added in any type or form which is suitable for human consumption. It is convenient to provide the calcium and potassium in the form of their gluconates, phosphates or hydrogen phosphates, and magnesium as the oxide or carbonate, chromium as chromium picolinate, selenium as sodium selenite or selenate, and zinc as zinc gluconate. Typically the amounts are:xe2x80x94sodium at 400 mg/liter, calcium at 100 mg/liter, chloride at 600 mg/liter, potassium at 200 mg/liter, magnesium at 75 mg/liter and phosphorus at 50 mg/liter, chromium at 125 xcexcg/liter, selenium at 125 xcexcg/liter and zinc at 15 mg/liter.
For liquid drinks in which the creatine is completely soluble, the amount of creatine (calculated as the monohydrate from hereon) per liter or per Kg of prepared composition may range from 1.5 g to 24 g with a preferred content of about 12 g per liter. The normal serving size is in the range 200-750 ml, providing about 2 to 7 g, preferably about 5 g of creatine. During the first 4 days of creatine supplementation the recommended consumption is about 2.0 liters per day, divided in 4 or 5 parts per day to achieve creatine saturation. This is followed by 1 serving of 250-750 ml per day containing about 2-3 g of creatine to provide a sufficient level of creatine to maintain saturation.
For suspensions of creatine in semi-liquid or other edible supporting matrices, the amount of creatine per 100 g may range from 1 to 80 g (calculated as creatine monohydrate from hereon) The preferred portion size is in the range 5 to 100 g providing between 2 to 10 g (preferably 5 g) of creatine. During the first four days of creatine supplementation the recommended consumption is a suspension containing 10 to 25 g per day divided into 4 or 5 parts per day to achieve maximum creatine elevation in the tissues. However lower doses over a longer period (e.g. 3 g daily for 4 weeks) will have the same effect. This is followed by one serving of suspension daily containing 3 to 5 g creatine to provide a maintenance level of creatine.
The invention also relates to a method of making the composition defined above. Thus, in a second aspect the invention provides a method of making a composition for human consumption, the method comprising the step of providing, in the same composition, creatine and sufficient creatinine to render the creatinine substantially stable (as herein defined) when the composition is mixed with an aqueous medium. Preferably the aqueous medium is water or an aqueous solution. The method will also normally include the step of providing water or an aqueous solution, preferably in sufficient amount so as to dissolve substantially all of the creatine and creatinine in the composition.
It will be apparent to those skilled in the art that the order of addition of the components to the composition is generally not significant, and any sequence of steps which provides the object of the invention will suffice. Thus, for example, solid creatine and solid creatinine may be added (simultaneously or separately) to water or an aqueous medium; or water or an aqueous medium may be added to solid creatine and/or creatinine.
Accordingly, in one embodiment the second aspect of the invention provides a method of preparing a creatine containing composition for human consumption in which the creatine is substantially stable (as herein defined), the method comprising the steps of: providing a solution of creatine; and subjecting the solution of creatine to suitable conditions so as partially to convert the creatine to creatinine, thereby forming sufficient creatinine to render the creatine in the resulting composition substantially stable (as herein defined). The method typically will comprise the further step of packaging the composition in suitable containers e.g. glass or plastic bottles, foil sachets, aluminium cans etc.
Preferably the method is such that subjecting the solution of creatine to suitable conditions involves heating the solution above average ambient temperature. In one preferred method, the solution is heated to 90xc2x0 C. for 30 minutes.
In a third aspect the invention provides a method of preparing a creatine containing composition for human consumption in which the creatine is substantially stable (as herein defined), the method comprising the steps of: providing a solution of creatine; providing a solution of creatinine; and mixing the solutions so as to form a resulting composition in which there is sufficient creatinine to render the creatine substantially stable (as herein defined).
In this method the pH of the solution of creatinine is preferably lower than the pH of the solution of creatine. Desirably the pH of the solution of creatinine is in the range 2 to 3, and the pH of the solution of creatine is preferably in the range 4.5 to 7 with adjustment, if necessary, of the final pH to the desired level.
In a fourth aspect the invention provides a method of preparing a creatine containing composition for human consumption in which the creatine is substantially stable (as herein defined), the method comprising the steps of: providing solid creatine; providing solid creatinine; and mixing the two solids so as to provide a resulting composition which, when dissolved in aqueous solution, provides a composition in which there is sufficient creatinine to render the creatine substantially stable (as herein defined). Typically this method will further comprise the step of adding sufficient water or aqueous solvent to substantially dissolve the resulting composition. If desired the water or aqueous solvent may be pre-sterilised by heat treatment and/or filtration.
In a fifth aspect, the invention provides a method of preparing a creatine containing composition for human consumption in which the creatine is substantially stable (as herein defined), the method comprising the steps of: providing solid creatine and solid creatinine, or an aqueous solution of creatinine, the creatinine being in sufficient quantity to render the creatine substantially stable (as herein defined); mixing the solid creatine with the solid creatinine or aqueous solution of creatinine; and adding to the mixture an edible supporting matrix.
Advantageously, performance of the methods of the second, third, fourth or fifth aspects will result in a composition in accordance with the first aspect defined above.